Herbal meds/contraindicated in immunomodulation/chemotherapy

[Mike Bartolatz]

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Herbal meds and their immune effects/ contraindicated
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concurrent use of immunodulatory agents and many herbal medicines can cause DRASTIC consequences:

Tables for:
Acute Renal Transplant Rejection Possibly Related to Herbal Medications

[Am J Transplant 3(12):1608-1609, 2003. © 2003 Blackwell Publishing]


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Table 1. Herbal Medications and Their Immune Effects


Grapefruit Vitamin C source Increases bioavailability of many medications
St John's Wort Depression Decreases cyclosporine levels by effecting metabolism or absorption, or both
Echinacea Natural cold relief and immune booster Increases white blood cell counts
Astragalus Natural cold relief and immune booster Stimulates T cells
Ginseng Stimulates immune glands Unknown
Licorice root Stimulates immune glands Effects aldosterone and interferon levels
Pau d'arco Anti-inflammatory Anti-oxidant
Alfalfa Anti-inflammatory for arthritis Interferes with nitric oxide formation and has a variety of effects on lymphocytes
Zinc Cold relief Antiviral, possibly by stimulating interferon production

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From American Journal of Transplantation

Acute Renal Transplant Rejection Possibly Related to Herbal Medications
Posted 01/22/2004

Timothy D. Light; Jimmy A. Light

Abstract
Use of herbal and alternative medications in the United States is increasing. Many of these medications have unknown mechanisms of actions, and possible metabolic interactions with prescribed medications. We report a case of late acute rejection after exposure to two popular herbal medications.

Case Report
Herbal medications and health supplements are frequently used by the general public to help improve health and well being.[1] These medications are viewed as healthy and natural by patients and by many practitioners. Patients might not volunteer using such medications for multiple reasons: they might not recognize them as important medications, or they might fear offending the physician because of the 'alternative' approach. Most these medications are neither well understood nor studied in terms of pharmacology, drug interactions, side-effects, or efficacy.

A 59-year-old Caucasian female received a cadaveric renal transplant 16 years before this admission. Her renal failure was a result of poststreptococcal glomerulonephritis. She had been maintained on azathioprine 50 mg qd, and cyclosporine 75 mg bid, with trough levels of 100-150 mg/dL. She has been steroid-free for more than 10 years. Her baseline creatinine had been 1.1-1.4 mg/dL. She had never had acute rejection, nor any infectious complications except a severe viral infection within the first several weeks post transplant.

Six months (June 2002) before admission, in situ ductal breast cancer was diagnosed She was treated with lumpectomy, radiation, and cessation of estrogen supplementation. She underwent severe menopausal symptoms, and on the advice of her gynecologist started taking alfalfa and black cohosh supplements in October 2002 to alleviate her symptoms. Approximately 4 weeks later her serum creatinine increased to 1.9 mg/dL despite unchanged cyclosporine levels. In the subsequent 2 weeks her serum creatinine increased to 2.9 mg/dL (Figure 1), and she was referred for evaluation.

Figure 1. (click image to zoom) Cyclosporine trough level and serum creatinine concentration.



A transplant renal biopsy demonstrated severe acute rejection with vasculitits (Figure 2). She was treated with anti-T-cell immunoglobulin and steroids with partial improvement in her renal function.

Figure 2. (click image to zoom) Transplant renal biopsy with Banff II acute rejection.




January 30, 2004


Acute Renal Transplant Rejection Possibly Related to Herbal medications





Discussion
Most reports in the transplant literature regarding herbal medications and immunosuppression describe metabolic derangements affecting calcineurin inhibitor levels (Table 1). Grapefruit juice increases the bioavailability of cyclosporine, presumably by inhibiting intestinal CYP IIIA4 activity. St John's Wort decreases cyclosporine levels by decreasing absorption or increasing metabolism.[1,5,6,8,9] Cyclosporine levels were not affected in this patient, so the mechanism of rejection was presumably different.

Black cohosh (Cimicifuga Racemosa) is commonly used for menopausal symptoms. No immunologic or anti-inflammatory claims were discovered upon review of many herbal and naturopathic resources. No medline literature addresses any immune-modulating effects.

Alfalfa (Medicago Sativa) has many reputed effects described in the alternative medical literature. Alfalfa has been well studied in the allergy and rheumatology field because of exacerbating symptoms in Lupus patients. l-canavanine (a constituent of alfalfa) has been studied in vitro and in a variety of human and animal models as a potent T-cell activator.[2-5] Supplementation with arginine (which competes with l-canavanine) has been shown to increase transplant graft survival in animals.[7] Alfalfa administration may have caused immunostimulation and contributed to the acute rejection witnessed in this patient who had stable renal function for many years on low-dose immunosuppression.

Physicians should diligently review medications and body systems to elicit information that patients might not volunteer. Patients and other providers should be warned against adding new medications without fully investigating potential drug interactions. Close medical supervision is mandatory after any medication changes. Control of herbal medications is needed to protect patients who depend on suppressed immune systems to maintain organ function. Structured herbal medication research is needed to identify potential new therapies.


Corresponding author: Timothy D. Light, timlightmd@aol.com

Timothy D. Light, Jimmy A. Light, Section of Transplant, Department of Surgery, Washington Hospital Center, Washington, DC



Am J Transplant 3(12):1608-1609, 2003. © 2003 Blackwell